Human papillomaviruses (HPVs) are a group of more than 200 related viruses. More than 40 HPV types can be easily spread through direct sexual contact, from the skin and mucous membranes of infected people to the skin and mucous membranes of their partners. They can be spread by vaginal, anal, and oral sex (1). Other HPV types are responsible for non-genital warts, which are not sexually transmitted.

Sexually transmitted HPV types fall into two categories:

Low-risk HPVs, which do not cause cancer but can cause skin warts (technically known as condylomata acuminata) on or around the genitals and anus. For example, HPV types 6 and 11 cause 90% of all genital warts. HPV types 6 and 11 also cause recurrent respiratory papillomatosis, a less common disease in which benign tumors grow in the air passages leading from the nose and mouth into the lungs.

High-risk HPVs, which can cause cancer. About a dozen high-risk HPV types have been identified. Two of these, HPV types 16 and 18, are responsible for most HPV-caused cancers (2, 3).

HPV infections are the most common sexually transmitted infections in the United States. About 14 million new genital HPV infections occur each year (4). In fact, the Centers for Disease Control and Prevention (CDC) estimates that more than 90% and 80%, respectively, of sexually active men and women will be infected with at least one type of HPV at some point in their lives (5). Around one-half of these infections are with a high-risk HPV type (6).

Most high-risk HPV infections occur without any symptoms, go away within 1 to 2 years, and do not cause cancer. Some HPV infections, however, can persist for many years. Persistent infections with high-risk HPV types can lead to cell changes that, if untreated, may progress to cancer.

Which cancers are caused by HPV?

High-risk HPVs cause several types of cancer.

Cervical cancer: Virtually all cases of cervical cancer are caused by HPV, and just two HPV types, 16 and 18, are responsible for about 70% of all cases (7, 8).

Anal cancer: About 95% of anal cancers are caused by HPV. Most of these are caused by HPV type 16.

Oropharyngeal cancers (cancers of the middle part of the throat, including the soft palate, the base of the tongue, and the tonsils): About 70% of oropharyngeal cancers are caused by HPV. In the United States, more than half of cancers diagnosed in the oropharynx are linked to HPV type 16 (9).

Rarer cancers: HPV causes about 65% of vaginal cancers, 50% of vulvar cancers, and 35% of penile cancers (10). Most of these are caused by HPV type 16.

High-risk HPV types cause approximately 5% of all cancers worldwide (11). In the United States, high-risk HPV types cause approximately 3% of all cancer cases among women and 2% of all cancer cases among men (12).

Who gets HPV infections?

Anyone who has ever been sexually active (that is, engaged in skin-to-skin sexual conduct, including vaginal, anal, or oral sex) can get HPV. HPV is easily passed between partners through sexual contact. HPV infections are more likely in those who have many sex partners or have sex with someone who has had many partners. Because the infection is so common, most people get HPV infections shortly after becoming sexually active for the first time (13, 14). A person who has had only one partner can get HPV.

Someone can have an HPV infection even if they have no symptoms and their only sexual contact with an HPV-infected person happened many years ago.

Can HPV infections be prevented?

People who are not sexually active almost never develop genital HPV infections. In addition, HPV vaccination before sexual activity can reduce the risk of infection by the HPV types targeted by the vaccine.

The Food and Drug Administration (FDA) has approved three vaccines to prevent HPV infection: Gardasil®, Gardasil® 9, and Cervarix®. These vaccines provide strong protection against new HPV infections, but they are not effective at treating established HPV infections or disease caused by HPV (15, 16).

Correct and consistent condom use is associated with reduced HPV transmission between sexual partners, but less frequent condom use is not (8). However, because areas not covered by a condom can be infected by the virus (7), condoms are unlikely to provide complete protection against the infection.

Can HPV infections be detected?

HPV infections can be detected by testing a sample of cells to see if they contain viralDNA or RNA.

Several HPV tests are currently approved by the FDA for three cervical screening indications: for follow-up testing of women who seem to have abnormal Pap test results, for cervical cancer screening in combination with a Pap test among women over age 30, and for use alone as a first-line primary cervical cancer screening test for women ages 25 and older.

The most common HPV test detects DNA from several high-risk HPV types in a group, but it cannot identify the specific type(s) that are present. Other tests do tell in addition whether there is DNA or RNA from HPV types 16 and 18, the two types that cause most HPV-associated cancers. These tests can detect HPV infections before abnormal cell changes are evident, and before any treatment for cell changes is needed.

There are no FDA-approved tests to detect HPV infections in men. There are also no currently recommended screening methods similar to a Pap test for detecting cell changes caused by HPV infection in anal, vulvar, vaginal, penile, or oropharyngeal tissues. However, this is an area of ongoing research.

What are treatment options for HPV-infected individuals?

There is currently no medical treatment for persistent HPV infections that are not associated with abnormal cell changes. However, the genital warts, benign respiratory tract tumors, precancerous changes at the cervix, and cancers resulting from HPV infections can be treated.

Methods commonly used to treat precancerous cervical changes include cryosurgery (freezing that destroys tissue), LEEP (loop electrosurgical excision procedure, or the removal of cervical tissue using a hot wire loop), surgical conization (surgery with a scalpel, a laser, or both to remove a cone-shaped piece of tissue from the cervix and cervical canal), and laser vaporization conization (use of a laser to destroy cervical tissue).

Treatments for other types of benign respiratory tract tumors and precancerous changes caused by HPV (vaginal, vulvar, penile, and anal lesions) and genital warts include topical chemicals or drugs, excisional surgery, cryosurgery, electrosurgery, and laser surgery. Treatment approaches are being tested in clinical trials, including a randomized controlled trial that will determine whether treating anal precancerous lesions will reduce the risk of anal cancer in people who are infected with HIV. More information about the treatment of genital warts can be found in the Centers for Disease Control and Prevention (CDC) Sexually Transmitted Diseases Treatment Guidelines, 2010.

HPV-infected individuals who develop cancer generally receive the same treatment as patients whose tumors do not harbor HPV infections, according to the type and stage of their tumors. However, people who are diagnosed with HPV-positive oropharyngeal cancer may be treated differently than people with oropharyngeal cancers that are HPV-negative. Recent research has shown that patients with HPV-positive oropharyngeal tumors have a better prognosis and may do just as well on less intense treatment. Ongoing clinical trials are investigating this question (17, 18).

How does high-risk HPV cause cancer?

HPV infects epithelial cells. These cells, which are organized in layers, cover the inside and outside surfaces of the body, including the skin, the throat, the genital tract, and the anus.

Once HPV enters an epithelial cell, the virus begins to make the proteins it encodes. Two of the proteins made by high-risk HPVs (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death.

Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results. As the persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth, leading to the formation of an area of precancerous cells and, ultimately, a cancerous tumor.

Other factors may increase the risk that an infection with a high-risk HPV type will persist and possibly develop into cancer (19). These include:

Researchers believe that it can take between 10 and 30 years from the time of an initial HPV infection until a tumor forms. However, even when severely abnormal cells are seen on the cervix (a condition called cervical intraepithelial neoplasia 3, or CIN3), these do not always lead to cancer. The percentage of CIN3 lesions that progress to invasive cervical cancer has been estimated to be 50% or less (20).

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